Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells.
A component of fungus Thielavia minor, OPC-15161, has been shown to inhibit the proliferation and extracellular matrix production of extracellular matrix-producing mesangial cells in the kidney in vivo. In this study, we examined the effects of OPC-15161 on the proliferation and extracellular matrix production of rat cultured hepatic stellate cells (HSCs). To determine the effect of OPC-15161 on proliferation of HSCs, the cell number and the uptake of [3H]thymidine were investigated in the presence and absence of interleukin-1beta (IL-1beta). IL-1beta significantly increased the uptake of [3H]thymidine in the HSCs, and the addition of OPC-15161 inhibited the uptake in a dose-dependent manner. The cell number of HSCs was also increased by IL-1beta, which was inhibited by OPC-15161. Production of extracellular matrix by OPC-15161 was studied by the production of [3H]-hydroxyproline in the presence and absence of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 significantly increased the production of [3H]-hydroxyproline in the cells, whereas the addition of OPC-15161 inhibited this effect dose dependently. We also investigated the effects of OPC-15161 on Ca2+ mobilization and measured D-myo-inositol 1,4,5-triphosphate (IP3) in the HSCs. IL-1beta induced the increase of intracellular Ca2+ and IP3 concentrations in the HSCs, which were decreased by OPC-15161. Based on these results, we conclude that OPC-1 5161 inhibited the proliferation and production of hydroxyproline in cultured rat HSCs, and thus, it may have a role in prevention of liver fibrosis in vivo.
Sugawara
H
H
Second Department of Medicine, Kurume University School of Medicine, Japan.
Ueno
T
T
Torimura
T
T
Inuzuka
S
S
Tanikawa
K
K
D000818:Animals; D001230:Aspergillus / Q000737:chemistry*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D006131:Growth Inhibitors / Q000633:toxicity*; D006909:Hydroxyproline / Q000096:biosynthesis / Q000187:drug effects; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011719:Pyrazines / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D006131:Growth Inhibitors; D011719:Pyrazines; C067708:OPC 15161; D015544:Inositol 1,4,5-Trisphosphate; D006909:Hydroxyproline; D002118:Calcium